The objectives of the proposed research project are to investigate the physiological mechanisms of glucose homeostasis in the neonate and child as compared to the adult and the pathophysiology of these mechanisms in hypoglycemic disorders. Studies are also directed towards a better understanding of abnormal carbohydrate metabolism in diabetes mellitus. The emphasis of this investigation is on substrate availability, integrity of hepatic glucoregulatory enzymatic pathways and hormonal modulation of the above. The study primarily involves the simultaneous and sequential measurement of circulating concentrations of glucose, lactate, pyruvate, beta-hydroxybutyrate, acetoacetate, amino acids, insulin, glucagon, growth hormone, catecholamines and cortisol in humans and animals with disordered carbohydrate metabolism as a means of further understanding the basic biochemical defect(s). With new insight and definition of the specific etiology of various hypoglycemic disorders, and further understanding of the pathophysiology of diabetes mellitus, more rational approaches to therapy will, hopefully, be developed. BIBLIOGRAPHIC REFERENCES: Leichter, S.B., Pagliara, A.S., Grieder, M.H., Pohl, S., Rosai, J. and Kipnis, D.M.: Uncontrolled diabetes mellitus and hyperglucagonemia associated with an islet cell carcinoma. Amer. J. Med. 58:285, 1975. Pagliara, A.S., Stillings, S.N., Haymond, M.W., Hover, B., and Matschinsky, F.M.: Insulin and glucose as modulators of the amino acid induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. J. Clin. Invest. 55: 244, 1975.